The overall goal of this proposal is to understand the role of resident pulmonary phagocytic cells in the selective induction of Th2 responses to inhaled protein antigens. Several studies, including our own, have shown that the lung microenvironment favors Th2 priming. Furthermore, resident DC-like cells from the respiratory tract preferentially induce Th2 differentiation. In this application, we will test the direct role of pulmonary phagocytic cells in the induction of Th2 immunity. Underlying the proposal are two hypotheses. First, the lung phagocytes that take up inhaled antigens have many features of immature dendritic cells in that they are phagocytic and efficient at antigen uptake, express low densities of MHC class II, and do not express IL-12. However, in contrast to immature dendritic cells at other sites, they do express B7-1. We speculate that the combination of B7 expression together with other attributes of immature dendritic cells such as their expression of low density MHC class II complexes and their inability to secrete IL-12 will lead to preferential Th2 priming. Second, without maturational signals provided by inflammatory stimuli, protein antigens do not activate the dendritic cells to mature. Thus, priming of naive CD4 T cells may occur in the lung and not the draining lymph nodes, as is currently thought. These hypotheses will be tested in two specific aims: 1) to identify and characterize antigen-containing cells (potential APC) after exposure to inhaled antigen, and 2) to determine if the maturational status of the antigen loaded respiratory cells regulates the type of CD4 T cell response generated. Using transgenic mice expressing reporter genes selectively expressed, we will follow dendritic cell, CD4 T cell interaction in vivo monitoring IL-4 gene expression.